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Biomedical subjects

G Tremblay

Publications and source records attributed to G Tremblay.

At least 37 records · Page 2Linked to original sources

Increased interferon-gamma mRNA expression following alloincompatible myoblast transplantation is inhibited by FK506.

Myoblasts from C57BL/10SnJ+/+ were transplanted in major histocompatibility complex (MHC)-compatible mice (i.e., C57BL10SnJ+/+ and C57BL/10SnSc mdx/mdx) and in MHC-noncompatible (BALB/c+/+) mice. The recipients were killed 1-21 days after transplantation. C57BL10SnJ+/+ myoblasts were also transplanted in a few BALB/c+/+ mice treated with FK506 and killed 7 days thereafter. Our results showed that after MHC-noncompatible transplantation, interferon-gamma (IFN-gamma) mRNA expression is increased from day 5 to day 21, indicating the presence of a cellular immune reaction. Short-term immunosuppressive treatment with FK506 inhibited the transcription of IFN-gamma mRNA compared with that in untreated mice. Myoblast-specific antibodies were also detected 2 and 3 weeks after MHC-incompatible transplantation, indicating that the cellular immune reaction, revealed by the increase in IFN-gamma, was followed by a humoral reaction.

Animals↗

Long-term stability of diagnosis and symptom dimensions in a systematic sample of patients with onset of schizophrenia in childhood and early adolescence. I: nosology, sex and age of onset.

BACKGROUND: Little is known about the long-term outcome of schizophrenia that has its onset during childhood and early adolescence (early-onset schizophrenia, or EO-SZ). Whether or not EO-SZ is an aetiologically separate form of schizophrenia (SZ) is unresolved. METHOD: The study was a 14.8-year follow-up, using methods such as systematic sampling, evaluation of possible non-respondent bias, consensus best-estimate diagnoses (DSM-III-R) made independently in childhood and adulthood, measures of positive and negative dimensions, of non-psychotic behaviour disturbances (NPBD) and of developmental problems before the appearance of SZ. RESULTS: There was high stability of EO-SZ (n = 40) diagnoses (mean onset at 14.0 years) until adulthood (mean age at follow-up 28.8 years) but a lower stability of positive and negative schizophrenic dimensions. There was a poor outcome of EO-SZ, a strong over-representation of males but few gender differences, and no effect of age of onset on clinical features and outcome. CONCLUSIONS: EO-SZ taken as a whole shows no qualitative differences to adult-onset SZ. However, a distinction through the onset of preschizophrenic developmental problems or NPBD might be a way to investigate heterogeneity within EO-SZ.

Adolescent↗

Long-term stability of diagnosis and symptom dimensions in a systematic sample of patients with onset of schizophrenia in childhood and early adolescence. II: Postnegative distinction and childhood predictors of adult outcome.

BACKGROUND: The aim of this study was to verify the presence and stability across life of the positive/negative distinction in early-onset schizophrenia (EO-SZ) through a longitudinal factor analysis of the schizophrenic dimensions, and to identify the factors predicting several indices of long-term outcome for EO-SZ. METHOD: Forty children consecutively referred for DSM-III-R schizophrenia (SZ) in a specific catchment area comprised the sample. RESULTS: Across a 14.8-year follow-up, longitudinal factor analysis identified two separate factors corresponding to the positive and negative symptom dimensions. We also observed that: the GAS rated over the last three years of adult illness and the severity of negative symptoms during the stabilised interepisode intervals in adulthood were the indices of adult outcome that were most easily predicted; and the best childhood predictors of adult outcome were premorbid functioning and severity of positive and negative symptoms during acute episodes. CONCLUSIONS: The presence of premorbid non-psychotic behaviour disturbances (NPBD) and premorbid developmental problems was not related to severity of outcome, in contrast to the former variables.

Adolescent↗

Human breast cancer: genetic alterations in the MET gene region.

OBJECTIVE: to test whether the MET gene at chromosome 7q31, which encodes a receptor protein (tyrosine kinase) related to normal histological differentiation, undergoes structural changes in breast cancer. A previous study reported somatic alterations detected as loss of heterozygosity (LOH) at this locus in breast cancer. DESIGN: Analysis of DNA from tumours and matched normal tissue by Southern blot hybridization with the metH probe; the tumours were also analysed for estrogen and progesterone receptors, ploidy and S phase, and protein expression of the MET and c-erbB-2 protooncogenes. PARTICIPANTS: Eighty-two patients with breast cancer. RESULTS: Fifty-three percent of the patients were informative for polymorphism with the metH marker. Somatic alterations of MET, consisting of LOH, were demonstrated in 22% of women who were informative and had breast cancer. No correlation was found between LOH of MET and conventional prognostic factors, or status for c-erbB-2 proto-oncogene expression. Estrogen-receptor status correlated with progesterone-receptor status, and S phase correlated with ploidy and size of the tumour. CONCLUSIONS: Somatic alterations of MET, detected as LOH with the metH probe, occur in 22% of informative patients. These alterations do not correlate with the prognostic factors established when the mastectomy is performed. It remains to be determined whether the patients' overall survival and disease-free survival rates are correlated with genetic alteration of MET.

Breast Neoplasms↗

Three distinct patterns of ventricular activation in infarcted human hearts. An intraoperative cardiac mapping study during sinus rhythm.

BACKGROUND: Comprehensive data based on single-beat analysis of the ventricular activation sequence during sinus rhythm in infarcted hearts are currently not available. It was the aim of our study (1) to measure and analyze these activation sequences on the epicardial surface of the right and left ventricles and on the left ventricular endocardial surface, and (2) to correlate specific activation patterns with the surface ECG. METHODS AND RESULTS: Isochronal maps were computed from 127 endocardial and epicardial unipolar electrograms recorded simultaneously during sinus rhythm in 45 post-myocardial infarction patients operated on for recurrent ventricular tachycardia (age, 57 +/- 10 years [mean +/- SD], left ventricular ejection fraction, 29 +/- 9%). Patients with bundle-branch block, but not with intraventricular conduction defects, were excluded. Data such as the timing of initial and terminal activation, the number of breakthroughs, the total activation time, and the number of ventricular segments without activation were measured and analyzed according to location of the myocardial infarction. The global epicardial activation was characterized in all patients by a widespread initial breakthrough on the anterior right ventricle (16 +/- 8 milliseconds after QRS onset), which was followed by one or two other breakthroughs in 65% of patients. Subsequently, three characteristic epicardial patterns of the activation spread were found: (1) radial, from the right to the left ventricle, found in all patients with inferoposterior myocardial infarction; (2) counterclockwise rotation, in which posteroseptal crossing preceded the anteroseptal crossing, found in 38% of patients with anterior myocardial infarction; and (3) pincerlike encirclement, in which both septal crossings and/or breakthroughs occurred nearly simultaneously and merged at the left ventricular free wall (typical for apical involvement in anterior and combined myocardial infarction). The simultaneous presence of multiple major activation wave fronts typically found in patients with the pincerlike activation pattern was reflected on the surface ECG by multiphasic, notched QRS complexes. Activation delay was observed in 89% of patients, and terminal activation was topographically related to myocardial infarction in 94% of patients. Delayed activation exceeding the surface QRS was observed in 11% and 31% of cases on the endocardium and epicardium, respectively. CONCLUSIONS: These results offer a solid basis for a more precise interpretation of a wide range of electrophysiological data and provide a framework for future investigations of surface ECG reflections of endocardial and epicardial activation patterns recorded in patients with chronic myocardial infarction.

Electrocardiography↗

Urokinase overproduction results in increased skeletal metastasis by prostate cancer cells in vivo.

We previously reported that urokinase (uPA) is produced by the human prostate cancer cell line, PC-3, and could function as a growth factor for cells of the osteoblast phenotype. To examine the role of uPA in metastasis to the skeleton and to extraskeletal sites, we have developed a homologous model of uPA overexpression in a rat prostate cancer cell line. Full length cDNA encoding rat (r) uPA was isolated and subcloned as a 1.4-kilobase XbaI-BspHI fragment in the sense and antisense orientation into the Moloney murine leukemia retroviral vector pYN. The control (pYN) and experimental (pYN-ruPA, pYN-ruPA-AS) plasmids were transfected into Dunning R 3227, Mat LyLu rat prostate carcinoma cells. Experimental clones expressing at least 5-fold higher (pYN-ruPA) or 3-fold lower (pYN-ruPA-AS) than controls were selected, and control and experimental cells were inoculated into the left ventricles of inbred male Copenhagen rats. Animals were sacrificed at timed intervals to examine the evolution of metastatic lesions. Control animals developed metastases to the lumbar vertebrae resulting in spinal cord compression and hind limb paralysis at 20-21 days postinoculation. Animals inoculated with cells overexpressing uPA developed hind limb paralysis significantly earlier (by day 14-15 postinoculation). Additionally, more widespread skeletal (ribs, scapula, and femora) metastases were seen. Serum from experimental animals showed a progressive elevation in alkaline phosphatase levels, and histological examination of lumbar metastases revealed markedly increased osteoblastic activity over that observed in control animals. In contrast to this, animals inoculated with cells underexpressing uPA developed hind limb paralysis significantly later (days 25-29 postinoculation) and displayed decreased tumor metastasis. These studies support a role for the catalytic domain of uPA in enhancing both skeletal and nonskeletal prostate cancer invasiveness and are consistent with a role for the growth factor domain of uPA in mediating an osteoblastic skeletal response.

Animals↗

Viral infection enhances lung response to Micropolyspora faeni.

Farmer's lung is an important form of hypersensitivity pneumonitis. It is believed to represent a delayed type allergic reaction to microorganisms found in moldy hay dust. The disease is prevalent in farmers from countries where, because of high humidity in the summer, molding of stored hay is unavoidable.

Animals↗

Human myoblast transplantation in immunodeficient and immunosuppressed mice: evidence of rejection.

Normal human myoblasts were cloned and transplanted in the tibialis anterior of immunodeficient nude and SCID mice and in mdx mice under different immunosuppressive treatments (cyclosporine A, CsA; antilymphocyte serum, ALS) or not immunosuppressed. This permitted us to show the interaction of the immune system in the myoblast transplantation. The graft success was assessed by verifying signs of humoral and cellular immune reactions and the presence of dystrophin produced by the fusion of the donor myoblasts. This study showed that clones of human myoblasts were able to fuse and produce dystrophin in injected muscles of immunodeficient mice and mdx mice receiving an effective immunosuppressive treatment (i.e., ALS+CsA). However, the same pool of human myoblasts injected in mdx mice inadequately immunosuppressed (i.e., CsA alone or ALS alone) triggered an immune reaction and was rejected. Cells expressing CD4 and CD8 antigens were observed in the injected muscles of mice treated with CsA alone. Therefore, evidence of humoral and cellular rejection was observed following human myoblasts transplantation.

Animals↗

Pace mapping using body surface potential maps to guide catheter ablation of accessory pathways in patients with Wolff-Parkinson-White syndrome.

BACKGROUND. A pace mapping technique using body surface potential maps (BSPMs) was developed to guide the positioning of an ablation catheter at the ventricular insertion point of accessory pathways (AP) in patients with the Wolff-Parkinson-White syndrome (WPW). METHODS AND RESULTS. The study was performed on 30 WPW patients. BSPMs were recorded with 63 leads distributed over the entire torso surface. The catheter used for radiofrequency ablation was first placed in the vicinity of the ventricular preexcitation site predicted by BSPMs recorded during the delta wave. BSPMs were then recorded during pacing with this catheter, the comparison between the preexcited and paced BSPMs indicated whether the pacing site was too anterior or posterior with respect to the preexcitation site, and the catheter was moved accordingly. This process was repeated until the preexcited and paced BSPMs were highly correlated (r > or = 0.8), and ablation then was attempted. It was possible to successfully ablate the AP in 28 patients after an investigation that lasted 54 +/- 44 minutes between the recording of the first paced BSPM and that of the BSPM paced at the successful ablation site. Patients with left free wall pathways needed less investigation time compared with patients with pathways of other locations (46 +/- 9 versus 100 +/- 25 minutes, p = 0.031). The sensitivity of BSPM pace mapping was assessed using pacing with a multipolar catheter, and significant changes were observed on the BSPMs for beats with pacing sites that were only 5 mm apart. CONCLUSIONS, BSPM pace mapping allowed us to achieve a 93% success rate with short investigation durations, provides significant information that cannot be obtained with the standard 12-lead ECG, is a self-correcting procedure that reduces the importance of BSPM alterations due to individual differences in the shape of the torso or heart, and is applicable only to patients with AP showing antegrade conduction.

Adolescent↗

Rat prostate adenocarcinoma cells disseminate to bone and adhere preferentially to bone marrow-derived endothelial cells.

Approximately 70% of patients with prostatic cancer develop bone metastases. Metastatic prostate adenocarcinomas are associated with high mortality rates and represent a leading cause of cancer-related deaths among males. To study the host-tumor interactions underlying the predilection of prostate cancer cells for skeletal bone, an experimental model was developed using rat Dunning carcinoma Mat-LyLu cells. Inoculations of these cells into the left ventricle of the heart led to the development of spinal metastases in 100% of inoculated animals. A subline of Mat-LyLu (Mat-LyLu-B5) was subsequently selected through the sequential inoculation of bone marrow-derived carcinoma cells into the left ventricle and was found to have an increased metastatic potential compared to the parental line. The possible role of tumor cell adhesion to host cells in the process of bone marrow colonization was then investigated in vitro using the metastatic line and primary cultures of rat bone marrow-derived stromal cells. It was found that the adhesion of the metastatic Mat-LyLu cells to a bone marrow stromal cell culture highly enriched for endothelial cells was significantly higher than the adhesion to other bone-derived cells, including nonendothelial bone marrow stromal cells (3.5x) and osteoblasts (1.7x). It was also significantly higher than the adhesion to rat fibroblasts (7x) and to hepatic endothelial cells (7.5x). The results suggest that the adhesion of prostate carcinoma cells to the bone marrow endothelium may play a role in their metastasis to bone.

Adenocarcinoma↗

Production of H2O2 by alveolar macrophages in experimental allergic alveolitis.

Experimental extrinsic allergic alveolitis (EAA) was induced in guinea pigs with Saccharopolyspora rectivirgula. Bronchoalveolar lavages were performed before inducing EAA (day 1, BAL 1), on day 23 (BAL 2), and on day 48 (BAL 3). The number of cells/ml in lavage fluid was increased at BAL 2 (4.79 x 10(6) and BAL 3 (4.29 x 10(6)) compared with BAL 1 (0.56 x 10(6)). The number of major cell types increased simultaneously, neutrophil becoming the predominant cell type over alveolar macrophages (AM). The production of H2O2 by AM was measured at the different phases of EAA. Adherent AM were either non-stimulated or triggered with phorbol myristate acetate (PMA), zymosan. S. rectivirgula opsonized with normal guinea pig serum (SRNS), or S. rectivirgula opsonized with guinea pig anti-S, rectivirgula serum (SRAS). Stimulated AM produced larger quantities of H2O2 than unstimulated cells, PMA being the most potent stimulus. At day 1, AM stimulated with S. rectivirgula and zymosan produced similar quantities of H2O2. After the induction of the disease, AM stimulated with S. rectivirgula produced larger quantities of H2O2 than with zymosan. Production of H2O2 by AM stimulated with S. rectivirgula or PMA, respectively, stayed the same at day 1 and 23, but increased sharply for both stimuli at day 48. There was no difference between H2O2 production by AM triggered with SRNS or with SRAS.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolitis, Extrinsic Allergic↗

Epicardial and endocardial mapping of ventricular tachycardia in patients with myocardial infarction. Is the origin of the tachycardia always subendocardially localized?

BACKGROUND: Left ventricular endocardial reentry is the conventional concept underlying surgery for ventricular tachycardia (VT). We assessed the incidences of patterns showing complete reentry circuits at either the subendocardial or subepicardial level and of patterns in which left ventricular endocardial mapping could only in part account for a reentrant mechanism. METHODS AND RESULTS: We retrospectively analyzed epicardial and left ventricular endocardial isochronal maps of 47 VTs induced in 28 patients with chronic myocardial infarction (inferior, 14 patients; anteroseptal, 14 patients). Electrograms were recorded intraoperatively from 128 sites with epicardial sock and transatrial left ventricular endocardial balloon electrode arrays. Given the methodology used in this study, the mapping characteristics of the tachycardias suggested five types of activation patterns: 1) complete (90% or more of VT cycle length) subendocardial reentry circuits in seven VTs (15%) and seven patients (25%), 2) complete subepicardial reentry circuits in four VTs (9%) and four patients (14%), 3) incompletely mapped circuits with a left ventricular endocardial breakthrough preceding the epicardial breakthrough in 25 VTs (53%) and 21 patients (75%), 4) incompletely mapped circuits with a left ventricular epicardial breakthrough preceding the endocardial breakthrough in three VTs (6%) and three patients (11%), and 5) a right ventricular epicardial breakthrough preceding the left ventricular endocardial breakthrough in eight VTs (17%) and seven patients (25%). After surgery, one type 3 VT and three type 5 VTs were reinducible. Thus, left ventricular endocardial reentry substrates (types 1 and 3) accounted for 68% of VTs, but substrates involving subepicardial (types 2 and 4) and deep septal layers (type 5) accounted for 32% of VTs. CONCLUSIONS: In a substantial number of VTs, a substrate localization that is at variance with the conventional concept can be detected by simultaneous epicardial and endocardial mapping and may require modification of the surgical approach conventionally aimed at endocardial layers.

Cardiac Pacing, Artificial↗

Respiratory health of workers exposed to swine confinement buildings only or to both swine confinement buildings and dairy barns.

Swine building workers (N = 488) and nonfarming neighborhood referents (N = 216) were enrolled in this study. There was a slight but significant increase in the prevalence of chronic bronchitis (17.49 versus 11.57%) and more evidence of airflow obstruction (forced expiratory volume in 1 s/forced vital capacity 0.75 versus 0.78) among the swine workers when they were compared with the referents. The subjects who spent more than 3 h/d in the swine buildings had a higher prevalence of chronic bronchitis (21.94 versus 13.25%) and airflow obstruction (forced expiratory volume in 1 s/forced vital capacity 0.75 versus 0.76) than those with shorter daily contact. Swine building only workers had no precipitins to antigens found in their environment and no clinical evidence of extrinsic allergic alveolitis. The number of years on the farm, dual exposure with dairy cattle, positive skin prick tests, type of piggery, and type of feeding did not add to the respiratory health impact of swine buildings.

Agricultural Workers' Diseases↗

Surface immunoglobulin-positive lymphoblastic lymphoma. A report of three cases.

Lymphoblastic lymphomas (LBL) are a morphologically homogeneous group of non-Hodgkin's lymphomas which are indistinguishable in tissue sections from acute lymphoblastic leukemia (ALL). Although initial immunologic studies of LBL suggested that these lymphomas are of the T-cell phenotype, investigations have recently described patients with LBL having pre-B-cell, "common" ALL, and natural killer cell phenotypes. The authors recently reported detailed immunophenotypic characteristics in 36 cases of LBL, including a single case of LBL with a surface immunoglobulin-positive B-cell phenotype. Three additional patients with LBL whose cells expressed monoclonal serum immunoglobulins are presented here. In addition, the neoplastic lymphocytes expressed several B-cell-associated antigens. The tumor cells in the single case tested were TdT-negative. Despite the unusual immunologic phenotype, the morphologic features in all three cases were characteristic of LBL. In addition to the previously reported single case, to the authors' knowledge these are the only reported cases of a previously unrecognized variant of LBL: surface immunoglobulin-positive, B-cell LBL.

Adolescent↗

Airborne microbial contents in two types of swine confinement buildings in Quebec.

Airborne microorganisms were isolated with a sampler in two types of swine confinement buildings (farrowing units and fattening units). Respirable (particles less than 5 microns) and total dust fractions were obtained. Samplings were repeated every 2 weeks for a total of 6 samplings per unit between January and April. The predominant microorganisms isolated were bacteria (up to 1.25 x 10(6) CFU/m3) with an important fraction in the respirable size range (up to 0.5 x 10(6) CFU/m3). Only small quantities of gram-negative bacteria, yeasts, and molds were found. Identification of the colonies isolated revealed a great diversity of microorganisms present in the air of the different buildings. Enterobacter agglomerans, Moraxella, Acinetobacter calcoaceticus, and Pseudomonas were the most frequently identified bacteria. Scopulariopsis, Aspergillus, Penicillium, and Candida were the most numerous fungi. Faenia rectivirgula, the causative agent of farmer's lung, was not a major contaminant. The results show some differences in airborne microbial contamination between farrowing and fattening units; the distinction, however, is not clear-cut and was observed only for the total bacteria. The level of airborne microbial contamination in swine units does not significantly vary as a function of the outside temperature. Some species of bacteria and fungi isolated in this study are known to induce extrinsic allergic alveolitis. Other fungi are known to be potentially pathogenic for man. The air of swine confinement buildings is highly contaminated with bacteria, yeasts, and molds at a level up to 1200 time higher than so-called "normal air."

Air Microbiology↗

Sequential bronchoalveolar lavages by endotracheal intubation in guineapigs.

We examined the feasibility of performing repeated bronchoalveolar lavage (BAL) on guineapigs. We also determined the influence of lavage volume on cell recovery in these animals, verified if the free cell populations were altered by repeated lavage, and compared the results with those obtained after euthanasia. Live animals were intubated orotracheally by direct vision laryngoscopy and lavaged, except for the last BAL which was done on isolated lungs after euthanasia. Each animal was lavaged weekly for 8 weeks: weeks 1-5 lavages were done with 5 aliquots of 2 ml of normal saline, week 6 with 3 aliquots of 1 ml, week 7 with 3 aliquots of 2 ml, and week 8 with 5 aliquots of 2 ml after euthanasia. The first 5 BAL gave similar results in volumes recovered, total number of cells, cell viability and differentials. The total cell yield of lavages 6 and 7 was less than that of the first 5 BAL and BAL 8; cell differentials with these smaller lavages were similar except for the percentage of neutrophils which was slightly higher than with the 10 ml lavage at week 3. The final lavage gave similar results as the first 5 BAL in terms of total cells recovered, cell viability, and differentials. We conclude that repeated BAL is feasible in live guineapigs, and that it gives a similar cells yield as lung lavage obtained after euthanasia.

Animals↗